Irisin alleviates steroid-induced vascular dysfunction by regulating the αVβ5-c-Abl-Caveolin-1 signaling pathway

Area of Science:

• Vascular Biology
• Bone Diseases
• Endocrinology

Background:

• Steroid-induced avascular necrosis of the femoral head (SANFH) results from glucocorticoid (GC)-induced endothelial cell (EC) injury and impaired blood flow.
• Irisin, an endothelial-protective myokine, interacts with integrin αVβ5. Phosphorylated Caveolin-1 (CAV-1) contributes to endothelial dysfunction.

Purpose of the Study:

• To investigate the roles of irisin and CAV-1 in SANFH.
• To elucidate the protective mechanisms of irisin in GC-induced vascular dysfunction relevant to SANFH.

Main Methods:

• Analysis of irisin and CAV-1 phosphorylation in human and mouse SANFH samples.
• Administration of irisin in a mouse model of SANFH.
• In vitro studies using cultured ECs to examine signaling pathways involving GC, irisin, integrin αVβ5, c-Abl, and CAV-1.

Main Results:

• Decreased irisin and increased CAV-1 phosphorylation were observed in SANFH samples.
• Irisin treatment reduced osteonecrosis, vascular abnormalities, and CAV-1 phosphorylation in mice.
• In vitro, irisin inhibited GC-induced c-Abl and CAV-1 phosphorylation via integrin αVβ5, preserving EC viability, angiogenesis, and migration.

Conclusions:

• Irisin demonstrates a protective effect against vascular dysfunction in SANFH.
• The mechanism involves irisin inhibiting GC-triggered c-Abl-CAV-1 phosphorylation through the integrin αVβ5 pathway.
• Irisin presents potential therapeutic applications for treating SANFH.